PubMed Health⌕ Search

Biomedical subjects

J Brady

Publications and source records attributed to J Brady.

At least 37 records · Page 2Linked to original sources
PubMed1998

Regulation of TNFalpha and TGFbeta-1 gene transcription by HIV-1 Tat in CNS cells.

Tat is a transcription transactivator produced by the human immunodeficiency virus type 1 (HIV-1) at the early phase of infection and plays a critical role in the expression and replication of the viral genome. This 86 amino acid protein, which can be secreted from the infected cells, has the ability to enter uninfected cells and exert its activity upon the responsive genes. Earlier results indicated that in addition to the HIV-1 promoter, Tat has the capacity to induce transcription of a variety of cellular genes. In this study, we demonstrate that exposure of cells from the central nervous system (U-87MG and SK-N-MC) and the lymphoid T cells (Jurkat) to highly purified Tat increases transcriptional activity of the reporter constructs containing the promoters from the transforming growth factor beta-1 (TGFbeta-1), the tumor necrosis factor alpha (TNFalpha), and the HIV-1 LTR. In addition, Tat treatment results in increased levels of TGFbeta-1 and TNFalpha mRNAs in these cells. Activation of the TGFbeta-1 and TNFalpha promoter constructs by Tat in U-87MG and SK-N-MC cells required amino acid residues 2 to 36 which spans the acidic and the cysteine-rich domains of Tat. In both CNS and lymphoid cells, the level of endogenous TGFbeta-1 mRNA was increased by mutant Tat protein containing amino acids 1 to 48 but not with a mutant Tat protein with a deletion between residues 2 to 36. TNFalpha mRNA level was increased by mutant Tat spanning residues 1 to 48 in U-87MG cells, but not in SK-N-MC and Jurkat cells. These observations suggest that activation of cellular and viral genes by Tat in various cells may be mediated by different pathways as evidenced by the requirements of the different regions of Tat. Activation of the TGFbeta-1 and TNFalpha promoters by wild-type Tat was severely affected by the mutant peptides spanning residues 2 to 36 and 1 to 48 suggesting that both truncated Tat peptides may function as dominant negative mutants over TNFalpha and TGFbeta-1 gene transcription. The importance of these findings in Tat-induced regulation of viral and cellular genes in various cell types is discussed.

Brain↗
PubMed1998

Cancer among first-degree relatives of probands with invasive and borderline ovarian cancer.

OBJECTIVE: The familial clustering of ovarian, breast, endometrial, colon; and prostate cancer was compared in first-degree relatives of probands with invasive and borderline ovarian cancer to determine coaggregation. METHODS: Probands (n=392), who had been patients in the Division of Gynecologic Oncology at Washington University, were ascertained consecutively. Family history on 2192 first-degree relatives was collected by personal interviews of the probands and other family members. Estimates of prevalence of cancers in first-degree relatives of the two proband groups were compared. Survival analysis was used to examine the age-at-onset distribution of each cancer in relatives of invasive probands versus relatives of borderline probands. RESULTS: Among the relatives were 24 cases of ovarian cancer, 46 cases of breast cancer, 13 cases of endometrial cancer, and 25 and 28 cases of colon and prostate cancer, respectively. There were no significant differences in the prevalence of any of these cancers in relatives of the invasive and borderline probands. Cumulative lifetime risk estimates did not differ between the relatives of the two groups for any cancers. Age-at-onset of ovarian cancer did not differ between probands with positive family histories of the five cancers and those with negative histories. The inability to reject the null hypothesis of no differences in the first-degree relatives of our two study groups might be from insufficient power to detect small differences, given our sample size. CONCLUSION: These results suggest that relatives of patients with invasive and borderline ovarian cancer might share similar cancer risks and age-at-onset distributions.

Age of Onset↗
PubMed1998

Interference due to haemolysis in routine photometric analysis--a survey.

To assess the affect of haemolysis on routine photometric methods used by participants in the Irish External Quality Assessment Scheme for Clinical Biochemistry (IEQAS) a sample was distributed with a supplied diluent containing haemoglobin. A sample of the same batch had previously been circulated as a normal distribution. Many analytes/methods were affected by the haemolysis. The range of values reported for each analyte was as follows. Albumin 34-48 g/L (baseline 37 g/L). Calcium 2.16-2.68 mmol/L (baseline 2.34 mmol/L). Urate 90-470 mumol/L (baseline 195 mumol/L). Creatinine 55-161 mumol/L (baseline 140 mumol/L). Glucose 4.1-5.6 mmol/L (baseline 4.8 mmol/L). Bilirubin 14-60 mumol/L (baseline 36 mumol/L). Urea 3.4-7.3 mmol/L (baseline 3.8 mmol/L). Iron 17.9-55.0 mumol/L (baseline 26.8 mumol/L). Inorganic phosphorus 0.22-2.41 mmol/L (baseline 1.59 mmol/L). Cholesterol 3.0-5.9 mmol/L (baseline 4.1 mmol/L). In some situations the use of an appropriate blank may solve the problem, but it must be remembered that interference caused by haemoglobin may be more complex than merely spectral.

Albumins↗
PubMed1998

Odor-mediated host preferences of West African mosquitoes, with particular reference to malaria vectors.

The role of odors in mosquito host preferences was studied in a village near Ouagadougou, Burkina Faso. Two odor-baited entry-traps were put beside one another and a choice of host odor-laden air was blown out of them. Odors of a human and a calf (of similar mass) were drawn from two tents in which each was separately concealed. Allowances were made for trap position, differences in human-subject attractiveness, CO2 levels, and trap contamination with alternative host odors. Choices for the human-baited trap greater than the 0.5 random expectation were made by Anopheles gambiae s.l. (0.96) and An. pharoensis (0.68). The choices for the human-baited trap of Culex antennatus were significantly lower than 0.5 (0.25), whereas for the Cx. decens species group (0.56), the difference was not significant. Interpretation of the latter result was complicated by the significant effect of CO2 levels on the index. Species caught in low numbers but whose trap distribution showed a bias towards the human-baited trap were An. funestus (total numbers in the human-baited trap to the calf-baited trap = 9:0), Mansonia africana (17: 1), Aedes dalzieli (22:4), and Ae. hirsutus (13:1); species showing bias towards the calf-baited trap were An. rufipes (0:11), Cx. duttoni (0:17), and Cx. nebulosus (2:35). Mansonia uniformis was the only species distributed randomly between the two traps. Molecular identification of the An. gambiae s.l. samples revealed a marked difference in trap distribution: for the human-baited trap the ratio was 52% An. arabiensis to 48% An. gambiae s.s.; for the calf-baited trap, it was 92% An. arabiensis to 8% An. gambiae s.s.

Animals↗
PubMed1997

The class III POU factor Brn-4 interacts with other class III POU factors and the heterogeneous nuclear ribonucleoprotein U.

The class III POU proteins are expressed throughout the central nervous system, including the hypothalamus, where they are often co-localized. Presumably, these POU proteins (Brain-1, Brain-2, Brain-4 and SCIP) serve as transcriptional transactivators. That they are co-expressed in some neurons suggests that, if they were to form homomeric and heteromeric complexes with each other, depending on the particular combination, they might have different DNA-binding specificities and, thus, activate different genes. We used purified fusion proteins of the four class III POU proteins in far-western assays to show that the proteins can interact. We confirmed their interactions using a two-hybrid system. Both techniques indicate that the interaction occurs through the POU domain. The far-western technique also allowed us to identify a 120-kDa nuclear protein that interacts with Brain-4. Subsequent affinity purification and microsequencing identified the protein as the heterogeneous nuclear ribonucleoprotein U (hnRNP U). This result suggests another mechanism by which a POU protein can influence gene expression: by facilitating the processing of pre-mRNA whose transcription it has stimulated.

Amino Acid Sequence↗
PubMed1997

Professional practice. A framework for transition to a new culture.

The reorganization of healthcare systems has largely focused on the redesign of clinical management structures with little emphasis on the systems that are essential to support professional practice and quality of care. This article describes the unique process of designing a framework that clearly articulates the essential elements of professional practice. The framework was crucial in clarifying account-abilities and role relationships between the clinical management and professional practice structures in the design and implementation of a major reorganization at Toronto East General Hospital, a 400-bed community teaching hospital in Toronto, Canada.

Health Planning↗
PubMed1997

Astrocyte-specific expression of human T-cell lymphotropic virus type 1 (HTLV-1) Tax: induction of tumor necrosis factor alpha and susceptibility to lysis by CD8+ HTLV-1-specific cytotoxic T cells.

Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with a chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraperesis (HAM/TSP). Although the pathogenesis of this disease remains to be elucidated, the evidence suggests that immunopathological mechanisms are involved. Since HTLV-1 tax mRNA was colocalized with glial acidic fibrillary protein, a marker for astrocytes, we developed an in vitro model to assess whether HTLV-1 infection activates astrocytes to secrete cytokines or present viral immunodominant epitopes to virus-specific T cells. Two human astrocytic glioma cell lines, U251 and U373, were transfected with the 3' portion of the HTLV-1 genome and with the HTLV-1 tax gene under astrocyte-specific promoter control. In this study, we report that Tax-expressing astrocytic glioma transfectants activate the expression of tumor necrosis factor alpha mRNA in vitro. Furthermore, these Tax-expressing glioma transfectants can serve as immunological targets for HTLV-1-specific cytotoxic T lymphocytes (CTL). We propose that these events could contribute to the neuropathology of HAM/TSP, since infected astrocytes can become a source for inflammatory cytokines upon HTLV-1 infection and serve as targets for HTLV-1-specific CTL, resulting in parenchymal damage by direct lysis and/or cytokine release.

Astrocytes↗
PubMed1997

J.S. Kennedy (1912-1993): a clear thinker in behavior's confused world.

This is an account of the scientific life of John Stodart Kennedy, Fellow of the Royal Society; Emeritus Professor of Animal Behaviour at Imperial College, London; the holder of numerous scientific honors; and known to us all as JSK. He was not at heart an entomologist; his principal interest was in the integration of animal behavior, but he pursued that interest through a lifetime's study of locusts, aphids, and moths, especially in the context of how they integrated their flight behavior. Two features marked his science: an obsession with accurate, objective quantification of animals' behavioral responses through experimentation and a ruthless demolition of anthropomorphic analyses of behavioral causes. This biography is both a history of his scientific work and a tribute to a hugely admired colleague, research leader, and friend of some 30 years. The details of Kennedy's life were provided in part by his family, in part by the autobiographical notes he wrote for the Royal Society, and in part by his surviving colleagues from those early years; the last three decades are based on the author's personal knowledge and observation.

Animals↗
PubMed1996

A point mutation in the HIV-1 Tat responsive element is associated with postintegration latency.

Study of the mechanism of HIV-1 postintegration latency in the ACH2 cell line demonstrates that these cells failed to increase HIV-1 production following treatment with exogenous Tat. Reasoning that the defect in ACH2 cells involves the Tat response, we analyzed the sequence of tat cDNA and Tat responsive element (TAR) from the virus integrated in ACH2. Tat cDNA sequence is closely related to that of HIV LAI, and the encoded protein is fully functional in terms of long terminal repeat (LTR) transactivation. Cloning of a region corresponding to the 5'-LTR from ACH2, however, identified a point mutation (C37 -> T) in TAR. This mutation impaired Tat responsiveness of the LTR in transient transfection assays, and the measured defect was complemented in cells that had been treated with tetradecanoyl phorbol acetate or tumor necrosis factor type alpha (TNF-alpha). A compensatory mutation in TAR (G28 -> A), designed to reestablish base pairing in the TAR hairpin, restored wild-type Tat responsiveness. When the (C37 -> T) mutation was introduced in an infectious clone of HIV-1, no viral production was measured in the absence of TNF-alpha, whereas full complementation was observed when the infection was conducted in the presence of TNF-alpha or when a compensatory mutation (G28 -> A) was introduced into TAR. These experiments identify a novel mutation associated with HIV-1 latency and suggest that alterations in the Tat-TAR axis can be a crucial determinant of the latent phenotype in infected individuals.

Base Sequence↗
PubMed1996

Dilating the cervix medically to overcome an unsatisfactory colposcopy: 5 year follow up.

OBJECTIVE: To examine the long term results of placing a hydroscopic sponge in the cervix to expose high lesions and overcome an unsatisfactory colposcopic examination. STUDY DESIGN: Forty-one women presenting with their first abnormal smear but an unsatisfactory colposcopy were offered medical dilation of the cervix with Lamicel. These women had local ablative treatment and were followed for 5 years to establish the risk of recurrent disease after medical dilation. For comparison we measured the risk of recurrence after a cone biopsy performed as primary treatment for women attending a different hospital in the same city. RESULTS: Medical dilation was unacceptable or failed in 16 of the 41 women. It was initially successful at exposing the entire transformation zone and sparing 25 women a cone biopsy. Ten of these presented with recurrent disease requiring a cone biopsy within 5 years. Two cases were lost to follow up leaving 13 out of a total of 38 women who ultimately avoided a cone biopsy. The recurrent disease rate despite local treatment following medical dilation is 43%. The recurrent disease rate in the city following a cone biopsy is 20%. CONCLUSION: Although medical dilation of the cervix may permit lesions in the canal to be visualised, follow up is difficult and the risk of further disease is high. It is not recommended as a routine.

Biocompatible Materials↗
PubMed1996

Mosquito responses to carbon dioxide in a west African Sudan savanna village.

Mosquito responses to carbon dioxide were investigated in Noungou village, 30 km northeast of Ouagadougou in the Sudan savanna belt of Burkina Faso, West Africa. Species of primary interest were the main malaria vectors Anopheles gambiae s.s. and An.arabiensis, sibling species belonging to the An.gambiae complex. Data for An.funestus, An.pharoensis, Culex quinquefasciatus and Mansonia uniformis were also analysed. Carbon dioxide was used at concentrations of 0.04-0.6% (cf. 0.03% ambient concentration) for attracting mosquitoes to odour-baited entry traps (OBETs). The "attractiveness' of whole human odour was also compared with CO2 emitted at a rate equivalent to that released by the human bait. In a direct choice test with two OBETs placed side-by-side, the number of An.gambiae s.l. entering the trap with human odour was double the number trapped with CO2 alone (at the human equivalent rate), but there was no significant difference between OBETs for the other species of mosquitoes. When OBETs were positioned 20 m apart, again CO2 alone attracted half as many An.gambiae s.l. and only 40% An.funestus, 65% Ma.uniformis but twice as many An.pharoensis compared to the number trapped with human odour. The dose-response for all mosquito species was essentially similar: a linear increase in catch with increasing dose on a log-log scale. The slopes of the dose-response curves were not significantly different between species, although there were significant differences in the relative numbers caught. If the dose-response data are considered in relation to a standard human bait collection (HBC), however, the behaviour of each species was quite different. At one extreme, even the highest dose of CO2 did not catch more An.gambiae s.l. than one HBC. At the other extreme, the three highest doses of CO2 caught significantly more Ma.uniformis than did one HBC. An.pharoensis and Cx quinquefasciatus showed a threshold response to CO2, responding only at doses above that normally released by one man. An.funestus did not respond to CO2 alone at any dose in sufficient numbers to assess the dose response. Within the An.gambiae complex, An.arabiensis "chose' the CO2-baited trap with a higher probability than An.gambiae s.s. Also An.arabiensis, the less anthropophilic of the two species, was more abundant in CO2-baited OBETs than in human bait collections.

Animals↗
PubMed1995

Chromosomal localization of the genes for five zinc finger proteins expressed in mouse lens.

Based on sequence similarity to a consensus zinc finger domain, we have identified cDNAs encoding five proteins containing zinc finger nucleic acid binding motifs from a newborn mouse lens library. Utilizing these cDNAs as hybridization probes, we have mapped two of the corresponding genes to mouse Chr (chromosome) 11, two to mouse Chr 7, and one to mouse Chr 4 using two multilocus crosses. Because the zinc finger proteins encoded by these genes may be involved in regulating other genes that are expressed in lens, they can be considered candidates for the large number of yet unmapped cataract loci.

Animals↗
PubMed1994

Ifosfamide nephrotoxicity in paediatric cancer patients.

Ifosfamide is an alkylating agent which has been incorporated into frontline therapy for a number of malignant paediatric tumours. Recent data appears to suggest that tubular dysfunction may result from incorporation of this drug into chemotherapy schedules and that toxicity may be dose related. A detailed investigation of renal function was performed in a group of patients, ranging in age from 8 months to 15.9 years (median 8.6 years) with rhabdomyosarcoma (n = 11) and Ewing's sarcoma (n = 9) who were currently receiving (n = 4) or had completed ifosfamide (n = 16) therapy a mean of 16 months at the time of study. All but one patient demonstrated some degree of renal dysfunction and toxicity did not necessarily appear to be dose related. Implications for incorporation of this agent into future schedules for childhood sarcomas, which can expect to cure more than 60% of such children, must be addressed. The importance of ongoing monitoring is emphasised.

Adolescent↗